In recent years a number of adhesion and cytoskeletal molecules have been isolated and characterized at the molecular level. The identification of those molecules has provided a basis for a molecular understanding of the process of cell adhesion. The challenge now is to learn how these molecules are utilized for cell-cell and cell-substrate adhesions. This project examines two aspects of the adhesion phenomenon. First, methods have been developed for examining cell adhesion as a sequence of discrete events. One goal will be to characterize those events using known molecular probes. The events include initial binding with the substrate, collection of adhesion molecules at the site of contact, coupling the adhesion complex to the cytoskeleton, a strengthening of the adhesion over several orders of magnitude, and finally, the loss of the adhesion. The F9 teratocarcinoma cell line will be used for this study. F9 cells have the capacity to differentiate following treatment with retinoic acid. Prior to retinoic acid treatment the cells are epithloid. As the cells differentiate they become fibroblastic. Many adhesion molecules are known in the F9 system. The second aspect of this proposal, therefore, is to determine what molecular changes enable cells to undergo the predictable phenotypic conversion from an epithelial to a fibroblastic phenotype. The studies will be greatly aided by an adhesion mutant that is deficient in a specific integrin subtype. Adhesive properties of cells have a dramatic influence on cell behavior. Thus, tissue construction, morphogenesis, invasiveness and metastasis all have an adhesive requirement that directs or impinges upon cell behavior.